Obstetrics and Gynaecology - Research Publications

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Author: Lappas, Martha × Author: Walker, Susan × Author: Whitehead, Clare ×

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    Immune profiling of SARS-CoV-2 infection during pregnancy reveals NK cell and ?? T cell perturbations
    Habel, JR ; Chua, BY ; Kedzierski, L ; Selva, KJ ; Damelang, T ; Haycroft, ER ; Nguyen, THO ; Koay, H-F ; Nicholson, S ; McQuilten, HA ; Jia, X ; Allen, LF ; Hensen, L ; Zhang, W ; Sandt, CEVD ; Neil, JA ; Pragastis, K ; Lau, JSY ; Jumarang, J ; Allen, EK ; Amanant, F ; Krammer, F ; Wragg, KM ; Juno, JA ; Wheatley, AK ; Tan, H-X ; Pell, G ; Walker, S ; Audsley, J ; Reynaldi, A ; Thevarajan, I ; Denholm, JT ; Subbarao, K ; Davenport, MP ; Hogarth, PM ; Godfrey, DI ; Cheng, AC ; Tong, SYC ; Bond, K ; Williamson, DA ; McMahon, JH ; Thomas, PG ; Pannaraj, PS ; James, F ; Holmes, NE ; Smibert, OC ; Trubiano, JA ; Gordon, CL ; Chung, AW ; Whitehead, CL ; Kent, SJ ; Lappas, M ; Rowntree, LC ; Kedzierska, K (AMER SOC CLINICAL INVESTIGATION INC, 2023-03-22)
    Pregnancy poses a greater risk for severe COVID-19; however, underlying immunological changes associated with SARS-CoV-2 during pregnancy are poorly understood. We defined immune responses to SARS-CoV-2 in unvaccinated pregnant and nonpregnant women with acute and convalescent COVID-19, quantifying 217 immunological parameters. Humoral responses to SARS-CoV-2 were similar in pregnant and nonpregnant women, although our systems serology approach revealed distinct antibody and FcγR profiles between pregnant and nonpregnant women. Cellular analyses demonstrated marked differences in NK cell and unconventional T cell activation dynamics in pregnant women. Healthy pregnant women displayed preactivated NK cells and γδ T cells when compared with healthy nonpregnant women, which remained unchanged during acute and convalescent COVID-19. Conversely, nonpregnant women had prototypical activation of NK and γδ T cells. Activation of CD4+ and CD8+ T cells and T follicular helper cells was similar in SARS-CoV-2-infected pregnant and nonpregnant women, while antibody-secreting B cells were increased in pregnant women during acute COVID-19. Elevated levels of IL-8, IL-10, and IL-18 were found in pregnant women in their healthy state, and these cytokine levels remained elevated during acute and convalescent COVID-19. Collectively, we demonstrate perturbations in NK cell and γδ T cell activation in unvaccinated pregnant women with COVID-19, which may impact disease progression and severity during pregnancy.
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    Quantifying mRNA coding growth genes in the maternal circulation to detect fetal growth restriction
    Whitehead, CL ; Walker, SP ; Mendis, S ; Lappas, M ; Tong, S (MOSBY-ELSEVIER, 2013-08)
    OBJECTIVE: To examine whether mRNA circulating in maternal blood coding genes regulating fetal growth are differentially expressed in (1) severe preterm fetal growth restriction (FGR) and (2) at 28 weeks' gestation in pregnancies destined to develop FGR at term. STUDY DESIGN: mRNA coding growth genes were measured in 2 independent cohorts. The first was women diagnosed with severe preterm FGR (<34 weeks' gestation; n = 20) and gestation matched controls (n = 15), where the mRNA was measured in both maternal blood and placenta. The second cohort was a prospective longitudinal study (n = 52) of women whom had serial ultrasound assessments of fetal growth. mRNA coding growth genes in maternal blood were measured at 28 and 36 weeks in pregnancies with declining growth trajectories (ending up with term FGR; n = 10 among the 52 recruited) and controls who maintained normal growth trajectory (n = 15). RESULTS: In women with severe preterm FGR, there was increased expression of placental growth hormone (6.3-fold), insulin-like growth factors (IGF1, 3.4-fold; IGF2, 5.0-fold), IGF receptors (2.1-fold) and IGF binding proteins (3.0-fold), and reduced expression of ADAM12 (0.5-fold) in maternal blood (and similar trends in placenta) compared with controls (P < .05). Notably, at 28 weeks' gestation there was increased IGF2 (3.9-fold), placental growth hormone (2.7-fold), and IGF BP2 (2.1-fold) expression in maternal blood in women destined to develop FGR at term (P < .05). CONCLUSION: Measuring mRNA coding growth genes in maternal blood may detect unsuspected severe preterm FGR already present in utero, and predict term FGR when measured at 28 weeks' gestation.
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    Placental Specific mRNA in the Maternal Circulation Are Globally Dysregulated in Pregnancies Complicated by Fetal Growth Restriction
    Whitehead, CL ; Walker, SP ; Ye, L ; Mendis, S ; Kaitu'u-Lino, TJ ; Lappas, M ; Tong, S (ENDOCRINE SOC, 2013-03)
    CONTEXT: Fetal growth restriction (FGR) is a leading cause of perinatal mortality, yet no reliable screening test exists. Placental specific mRNA in the maternal circulation may reflect changes in the placental transcriptome in FGR and could be a novel biomarker for FGR. OBJECTIVE: The aim of the study was to identify placental specific RNA detectable in the maternal circulation and examine whether they are differentially expressed in severe preterm FGR. DESIGN: In silico screening was used to identify placental specific RNAs. Their expression in cases of severe FGR vs controls was examined in both maternal blood and placenta by microarray, RT-PCR, and in situ hybridization. RESULTS: Via in silico analysis, we identified 137 genes very highly expressed in the placenta relative to other tissues. Using microarray, we found that they were detectable in the maternal blood and were globally dysregulated with preterm FGR; 75 genes (55%) had a ≥1.5-fold differential expression compared to controls. Eight genes (ERVWE-1, PSG1, PLAC4, TAC3, PLAC3, CRH, CSH1, and KISS1) were validated by RT-PCR to be significantly increased in both maternal blood and placenta in a larger cohort of severe FGR compared to controls. In situ hybridization confirmed PAPPA2 and ERVWE-1 localized to the syncytiotrophoblast. CONCLUSION: There is global differential expression of placental specific mRNA in the maternal blood in pregnancies complicated by severe preterm FGR. Placental specific mRNA in maternal blood may represent a new class of biomarkers for preterm FGR.